横山 健介

BACKGROUND AND AIMS: Stenosis at pancreaticojejunal (PJ) anastomosis is a recognized adverse event after pancreaticoduodenectomy. Although double-balloon endoscopic retrograde cholangiopancreatography (DB-ERCP) can be used for management, this procedure is often technically challenging. METHODS: We describe a case in which complete obstruction of PJ anastomosis was successfully treated by identifying the anastomosis with contrast injection through a standard injection needle. RESULTS: Pancreatography was performed by puncturing the area suspected to be the anastomosis with a 25-gauge injection needle. After pancreatography, the anastomosis was dilated using a balloon catheter, and endoscopic nasopancreatic duct drainage was placed. No adverse events occurred. CONCLUSIONS: After DB-ERCP, pancreatic duct dilatation improved. Pancreatography and treatment of PJ anastomotic obstruction can be performed safely by puncturing the anastomotic site with an injection needle.

With accompanying video, Sakurai and colleagues described a peroral direct cholangioscopy technique using a double-balloon enteroscope to treat bile duct stones after Billroth II gastrectomy. Direct insertion of the enteroscope into the bile duct eliminated scope exchange, enabling precise device manipulation, broader accessory selection, and shorter procedure time.

BACKGROUND: IgG4-related disease is a rare autoimmune disorder characterised by tissue infiltration of IgG4-positive plasma cells, storiform fibrosis, elevated serum IgG4 concentrations, and increased risk of tumour complications. Previous genetic studies have implicated FCGR2B and HLA loci in susceptibility to IgG4-related disease; however, most relied on microarray-based genotyping and imputation, which have limited resolution in highly polymorphic and structurally complex regions. This study aimed to investigate genetic susceptibility to IgG4-related disease using comprehensive genomic variant analysis, including low-frequency and structural variants not readily captured by microarrays. METHODS: We conducted a genome-wide association study using whole-genome sequencing data in a two-set, subtype-stratified case-control design in the Japanese population. Set 1 included samples (cases) from patients with IgG4-related disease from 50 hospitals across Japan participating in the Japanese IgG4-related disease Working Consortium (recruited between Oct 27, 2008, and March 3, 2016) and previously sequenced Japanese population control samples. Set 2 included samples (cases) from patients with IgG4-related disease from eight hospitals of the Consortium (recruited between Aug 12, 2021, and Dec 20, 2023) and previously sequenced healthy individuals residing in the Tokyo metropolitan area (controls). No specific inclusion or exclusion criteria were applied to either cases and controls. We used whole-genome sequencing at depths of 15× or 30× using HiSeqX and NovaSeq platforms (Illumina; San Diego, CA, USA) to enable the inclusion of previously uncaptured single nucleotide polymorphisms and direct analysis of HLA amino acid residues. We investigated complement component 4 copy number variations using short-read sequencing data and established read-depth-based typing methods. People with lived experience of IgG4-related disease were not involved in the study. FINDINGS: This whole-genome sequencing study comprised of 2 sets. Set 1 included 646 patient samples (172 [26·6%] were female, 474 [73·4%] were male, and the mean age was 64·4 years [SD 11·4]) and 2254 population controls (1348 [59·8%] were female and 906 [40·2%] were male). Set 2 included 223 patient samples (78 [35·0%] were female, 145 [65·0%] were male, and the mean age was 63·5 years [10·9]) and 405 population controls (65 [16·0%] were female and 340 [84·0%] were male). All individuals were of Hondo Japanese ancestry. The average IgG4 concentration at diagnosis was 653·1 mg/dL (SD 596·3) in Set 1 and 543·5 mg/dL (603·5) in Set 2. We validated the FCGR2B (p=9·8 × 10-11) region as the susceptibility locus for IgG4-related disease. PTCH1 (p=3·8 × 10-8) and long non-coding RNA LOC102724227 were found to be specific susceptibility loci for Mikulicz's disease. We also confirmed the association between the HLA amino acid residue DRB1-GB-7 (p=1·1 × 10-19) with IgG4-related disease and identified two additional residues, A-GA2-9 (p=4·1 × 10-6) and DQB1-GB-82 (p=4·7 × 10-9), that were significantly associated with IgG4-related disease. In the joint-association analysis of complement component 4 copy number variation, C4A showed a protective association with IgG4-related disease (β=-0·127, p=7·9 × 10-3), whereas C4B was associated with an increased risk (β=0·151, p=1·9 × 10-2). A low level of linkage disequilibrium (r2<0·15) was observed between the C4A and C4B alleles and the identified HLA amino acid residues in the main island Japanese population. INTERPRETATION: C4 copy number variation, in addition to HLA and FCGR2B, was found to be a distinct genetic factor associated with IgG4-related disease susceptibility, illustrating the complex polygenic nature of the disease. Furthermore, the identification of PTCH1 and the long non-coding RNA LOC102724227 as Mikulicz's disease-specific susceptibility loci suggests that genetic heterogeneity might underlie the clinical diversity of IgG4-related disease, particularly with respect to the affected organs. FUNDING: The Japanese Ministry of Health, Labour, and Welfare, the Japanese Agency of Medical Research and Development, the Kyoto University Grant for Top Global University Japan Project, and the Kyoto University Division of Graduate Studies SPRING Program.

A 50-year-old man was diagnosed with type 1 autoimmune pancreatitis (AIP) following endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and a histopathological examination. After six months of untreated follow-up, the serum IgG4 level decreased, and the diffuse pancreatic enlargement improved; however, a pancreatic head mass became apparent. EUS-FNA of this mass revealed pancreatic ductal adenocarcinoma (PDAC) with IgG4-positive plasma cells. In addition, the resected specimen revealed PDAC, without any features of AIP. After pancreatoduodenectomy, AIP did not recur. The development of AIP in this case could be related to paraneoplastic syndrome.